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Faculty Detail    
Name JOHN M PARANT
  
Campus Address VH 252 Zip 0019
Phone  (205) 975-8469
E-mail  jparant@uab.edu
Other websites
     


Faculty Appointment(s)
Appointment Type Department Division Rank
Primary  Cell, Developmntl, & Integrative Biology  Cell, Developmntl, & Integrative Biology Professor
Center  Comprehensive Cancer Center  Comprehensive Cancer Center Professor

Graduate Biomedical Sciences Affiliations
Cancer Biology 
Cell, Molecular, & Developmental Biology 
Genetics, Genomics and Bioinformatics 
Pathobiology and Molecular Medicine 

Biographical Sketch 
Dr. Parant received a dual B.S, in Molecular genetics and Marine Biology from Florida Institute of Technology in 1993; he received his PhD in Cancer Genetics from University of Texas/MD Anderson Graduate school of Biomedical Sciences in 2003, working with Dr Lozano on in vivo models of Li Fraumeni syndrome and p53 regulation; he preformed his postdoctoral studies at the University of Utah/Huntsman Cancer Center in Dr. Yost’s lab establishing Zebrafish as a model system to study tumorigenesis and p53 function; in 2010 he joined UAB as a Assistant Professor in the department of Pharmacology and Toxicology

Society Memberships
Organization Name Position Held Org Link
American Association of Cancer Research  Member   
American Society of Cell Biology  Member   
Society for Developmental Biology  Member   
 



Research/Clinical Interest
Title
Animal Models of Genomic Instability, p53 Regulation, Cancer and Mitotic Dysfunction
Description
The overall focus of my lab is to understand the cause and consequence of genomic instability in human diseases. Cancer is one of the leading causes of mortality worldwide and 90% of all solid tumors display abnormal karyotypes. Chromosomal instabilities occur in 1 of 150 births and are the leading cause of miscarriages and birth defects in humans. Recent studies suggest that increased aneuploidy in neuronal progenitor cells is associated with neurological disease. We utilize animal models to further understand the in vivo consequence of genomic instability as they relate to human disease. We have taken a two prong approach: 1) model familial human diseases with genomic instability in experimentally amenable organisms through gene knockdown and ask key questions about function and mechanism; and 2) Design genetic screens to identify genes involved in various aspects of genomic instability. We use both zebrafish and mouse to achieve these goals. For many years I have been working on the regulation of the tumor suppressor p53, and its influence on genomic instability. Li Fraumeni (LFS) is an autosomal dominant cancer predisposition, in which 50% of carriers will develop tumors by the age of 30. P53 mutations are responsible for 60% of LFS families. We have developed animal models of LFS in both mouse and zebrafish, and utilize them to further understand p53 regulation, tumor suppression and response to DNA damage. We are also interested in what are the others genes responsible for LFS, and for this we have developed genetic screens in zebrafish to further identify such genes. We are also interested in the causes and consequences of aneuploidy. Through a genetic screen in zebrafish designed to identify mutants that display increased genomic instability, we have identified an animal model of Roberts Syndrome (RBS). RBS is an autosomal recessive developmental disorder, presenting with variable phenotypes including growth retardation, microcephaly, mental retardation, craniofacial defects and limb deformities. Cells from RBS patients display premature chromatid separation, aneuploidy and increased mitotic index. RBS is due to mutations in the gene ESCO2, however little is known about the function of ESCO2, beyond it is one of two vertebrate homologues of the yeast gene ECO1, which is required for sister chromatid cohesion. Thus, RBS represents a developmental disease due to increased aneuploidy resulting from defects in sister chromatid separation. We are continuing to use this zebrafish model to understand the cellular cause and consequence of aneuploidy due to defects in sister chromatid cohesion. In addition we are generating mouse conditional alleles of ESCO2 to further study tissue specific loss of ESCO2. We will continue to screen for genomic instability mutants, with an emphasis on mutants that display chromosome segregation defects as well as tumor predisposition. We also have a technology aspect to the lab. We have been developing the use of HRMA (High Resolution Melting curve Analysis), initially to genotype mutant animals and now to perform mutation scanning following genome editing with custom design TALEN or CRISPR nuclease to readily generate target mutations in specific genes. With this technology we have rapidly generated over 100 mutant alleles in over 50 genes, making our lab one of the premier genome editing labs.

Keywords
Zebrafish, Mouse, Li Fraumeni Syndrome, Roberts syndrome, Birth Defects, Tumor Suppressor, Genomic Instability, Aneuploidy, Mitosis, DNA damage, Cancer, and Apoptosis.